The proposed research consists of three groups of studies dealing with the control of breathing pattern. The first group of studies deals with the basic processes responsible for the sequential alternation between inspiration and expiration and involves detailed examination of the manner with which several inputs are handled by the respiratory oscillator. Special attention will be given to the threshold and integrative properties of the oscillator and to the reversibility of the observed effects. The properties, so defined, should help narrow the possible mechanisms by which respiratory rhythm may originate and clarify the mode of action of different respiratory modulating inputs. In the second group of studies, we shall examine the possible involvment of vagally mediated lung volume feedback in the control of breathing pattern in adult man. The use of selective changes in lung volume, and of the diaphragmatic activity, as the index of respiratory output, should permit confident interpretation of the results. The wide sppctrum of clinical conditions under which vagal influence will be tested should minimize the chance of systematic bias and permit correlations between the intensity of volume feedback and the existence of specific cardiopulmonary disorders. The third group of studies will utilize a combination of animal and human experiments to define the possible role of vagal nonmyelinated fibers in exercise limitation in healthy subjects and in patients with various cardiac and respiratory disorders. The approaches used in the second and third series of studies should help clarify the pathogenesis of tachypnea and dyspnea in patients with various cardiopulmonary disorders and may form the basis for specific diagnostic and therapeutic interventions in the management of the dyspneic patient.